Abstract 1320: Efficacy of fulvestrant-an estrogen receptor blocker-in Human SLE: A one-year double-blind placebo-controlled trial; clinical, serological, bone density, and molecular studies.
Authors:
NI Abdou, V Rider, C Greenwell, X Li, B Kimler.
Background:
In some murine lupus models, estrogen fuels the disease and androgens retard disease activity. 17-beta estradiol activates T cells, leading to increased calcineurin and CD154. Tamoxifen has been used in a small human SLE clinical trial, but adverse effects limit its use. This study asked about a different anti-estrogen approach, an estrogen receptor blocker. Fulvestrant blocks the effect of estradiol on T cells. In MRL lpr, it slowed SLE.
Methods:
20 SLE women with normal cycles were enrolled in a clinical trial of faslodex versus placebo monthly. There were 4 early dropouts (2 irregular menses, 1 headache, and on noncompliance) leading to 8 in each group.
Results:
The active group had a reduction in SLEDAI from 8.75 to 3.75 that persisted after study completion (3.5 at month 15). The active group had reduction in therapy: prednisone 5.75 to 2.5, plaquenil 400 to 200, azathioprine 125 to 100. There was no difference in serologies.
Estrogen levels increased from 53 to 90. There was no change in bone density.
Conclusion:
Faslodex was well tolerated and efficacious in this small trial.
Editorial Comment:
The increase in estrogen was unexpected and unexplained. Might this lead to hypercoagulability long-term? The study design was not completely clear: Why decrease Plaquenil in a 1 year study?
Bottom line:
If it helps SLE activity, AND is well tolerated, it deserves further study. It was not clear, however, that this would be done, given Dr. Abdou’s difficulties getting even this small study done.
